{
  "abstract": "To investigate the interplay between physical activity and cardiometabolic traits in human skeletal muscle, we characterized gene expression and chromatin accessibility across skeletal muscle cell types in 263 Finnish individuals from the FUSION Tissue Biopsy Study. We analyzed single-nucleus RNA-seq data (168,309 nuclei), single-nucleus ATAC-seq data (242,069 nuclei), and bulk RNA-seq data. Lower insulin resistance (HOMA-IR) and higher total physical activity were both associated with higher proportions of Type 1 nuclei and lower proportions of Type 2x nuclei. Traits typically associated with better health-lower trait values of cardiometabolic traits such as HOMA-IR and higher physical activity levels-were associated with higher expression of energy metabolism genes and lower expression of signaling pathway genes across muscle fiber types, total pseudobulk, and to some extent in bulk tissue. HOMA-IR and physical activity appeared to have inverse and partially independent directions of association when adjusting for both traits in the same model.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.",
    "Gilbert S. Omenn Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.",
    "Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.",
    "South Karelia Social and Health Care District, Wellbeing Services County of South Karelia, South Karelia, Finland.",
    "Institute of Clinical Medicine, Internal Medicine, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland.",
    "Department of Public Health, University of Helsinki, Helsinki, Finland.",
    "Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio, Finland.",
    "Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.",
    "Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.",
    "Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.",
    "University of Helsinki, Faculty of Medicine, Research Programs Unit, Clinical and Molecular Metabolism (CAMM), Helsinki, Finland.",
    "Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.",
    "Minerva Foundation Institute for Medical Research, Helsinki, Finland.",
    "Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 21,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Dan L Ciotlos"
    },
    {
      "affs": [
        0
      ],
      "name": "Sarah C Hanks"
    },
    {
      "affs": [
        1
      ],
      "name": "Arushi Varshney"
    },
    {
      "affs": [
        2
      ],
      "name": "Michael R Erdos"
    },
    {
      "affs": [
        1
      ],
      "name": "Nandini Manickam"
    },
    {
      "affs": [
        0
      ],
      "name": "Heather M Stringham"
    },
    {
      "affs": [
        1
      ],
      "name": "Peter Orchard"
    },
    {
      "affs": [
        0
      ],
      "name": "Erin M Hill-Burns"
    },
    {
      "affs": [
        2
      ],
      "name": "Narisu Narisu"
    },
    {
      "affs": [
        2
      ],
      "name": "Lori L Bonnycastle"
    },
    {
      "affs": [
        0
      ],
      "name": "Michael D Sweeney"
    },
    {
      "affs": [
        3
      ],
      "name": "Jouko Saramies"
    },
    {
      "affs": [
        4
      ],
      "name": "Markku Laakso"
    },
    {
      "affs": [
        5
      ],
      "name": "Jaakko Tuomilehto"
    },
    {
      "affs": [
        6,
        7,
        8
      ],
      "name": "Timo A Lakka"
    },
    {
      "affs": [
        9
      ],
      "name": "Karen L Mohlke"
    },
    {
      "affs": [
        0
      ],
      "name": "Michael Boehnke"
    },
    {
      "affs": [
        2
      ],
      "name": "Francis S Collins"
    },
    {
      "affs": [
        10,
        11,
        12
      ],
      "name": "Heikki A Koistinen"
    },
    {
      "affs": [
        0,
        1,
        13
      ],
      "name": "Stephen C J Parker"
    },
    {
      "affs": [
        0
      ],
      "name": "Laura J Scott"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6n56586ecc1g7.bib",
  "cited_by": 0,
  "doi": "10.1016/j.isci.2026.117293",
  "fulltext_url": "https://europepmc.org/articles/PMC13635265",
  "id": "6n56586ecc1g7",
  "issns": [
    "2589-0042"
  ],
  "landing_url": "https://europepmc.org/article/MED/42835133",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Muscle Physiology and Disorders"
    ]
  ],
  "openalex": "W7214208277",
  "pdf_url": "https://europepmc.org/articles/PMC13635265?pdf=render",
  "pmcid": "PMC13635265",
  "pmid": "42835133",
  "published": "2026-09-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6n56586ecc1g7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:10Z",
      "native_id": "MED:42835133",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42835133"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Muscle Physiology and Disorders",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Inverse directions of association of higher physical activity and higher insulin resistance with human skeletal muscle fiber-type gene expression.",
  "title_text": "Inverse directions of association of higher physical activity and higher insulin resistance with human skeletal muscle fiber-type gene expression.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:10Z",
  "url": "https://research.draconitic.com/paper/6n56586ecc1g7",
  "venue": "IScience",
  "versions": []
}